Production of Chemokines in the Lungs of Infants with Severe Respiratory Syncytial Virus Bronchiolitis

McNamara, Paul; Flanagan, Brian; Hart, C. A.; Smyth, Rosalind L

doi:10.1086/428855

Cited by 165 publications

(153 citation statements)

References 42 publications

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“…Chemokines released by RSV-infected epithelial cells are undoubtedly important in this infiltration. Indeed, increased expression of IL-6, CCL5, CXCL8, and CXCL10 was evident in bronchoalveolar or nasopharyngeal lavage of infants suffering from RSV infections, compared with age-matched controls (5,6,10). Our data on chemokine secretion are consistent with these clinical data.…”

Section: Discussionsupporting

confidence: 87%

“…The detection of goblet cell hyperplasia/metaplasia following RSV infection is consistent with excessive mucus production in RSV bronchiolitis (2,12). Finally, secretions of a panel of chemokines from RSV-infected WD-PBECs are similar to levels observed in RSV-infected infants (5,6,10).…”

Section: Discussionsupporting

confidence: 60%

“…A number of proinflammatory cytokines and chemokines, including CXCL8, CXCL10, and CCL5, correlate positively with disease severity (5,6). Gross and microscopic pathology from fatal cases of RSV infection are characterized by edema; small airway necrosis and sloughing; small airway plugs consisting of mucus, neutrophils, and sloughed epithelial cells; peribronchiolar and perivascular cuffing; interstitial infiltration and alveolar filling; and occasional giant cells (7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

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In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Villenave

Thavagnanam

Sarlang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

166

217

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Respiratory syncytial virus (RSV) is the major viral cause of severe pulmonary disease in young infants worldwide. However, the mechanisms by which RSV causes disease in humans remain poorly understood. To help bridge this gap, we developed an ex vivo/in vitro model of RSV infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs), the primary targets of RSV infection in vivo. Our RSV/WD-PBEC model demonstrated remarkable similarities to hallmarks of RSV infection in infant lungs. These hallmarks included restriction of infection to noncontiguous or small clumps of apical ciliated and occasional nonciliated epithelial cells, apoptosis and sloughing of apical epithelial cells, occasional syncytium formation, goblet cell hyperplasia/metaplasia, and mucus hypersecretion. RSV was shed exclusively from the apical surface at titers consistent with those in airway aspirates from hospitalized infants. Furthermore, secretion of proinflammatory chemokines such as CXCL10, CCL5, IL-6, and CXCL8 reflected those chemokines present in airway aspirates. Interestingly, a recent RSV clinical isolate induced more cytopathogenesis than the prototypic A2 strain. Our findings indicate that this RSV/WD-PBEC model provides an authentic surrogate for RSV infection of airway epithelium in vivo. As such, this model may provide insights into RSV pathogenesis in humans that ultimately lead to successful RSV vaccines or therapeutics.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 60%

mentioning

confidence: 99%

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In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Villenave

Thavagnanam

Sarlang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

166

217

View full text Add to dashboard Cite

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“…Recent studies have demonstrated that inflammatory mediators play essential roles in enhancing respiratory viral pathologies [15][16][17][18][19]; however, several of these mediators have not yet been identified. The contribution of host immune responses to the pathologies observed during respiratory viral infections opens up the potential for therapeutic alternatives based on the suppression of pathogenic immune response.…”

Section: Introductionmentioning

confidence: 99%

Distinctive and critical roles for cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in mice

Simon

Sasaki

Ichii

et al. 2011

Microbes and Infection

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Overall, DBA/2J mice exhibited a dysregulated hyper-inflammatory cytokine/chemokine cascades that does not limit viral spread resulting in a predisposition to severe lung pathology. This response is similar to severe human respiratory paramyxovirus infections, which will serve as a model for the elucidation of hyper-immune inflammatory response that result to severe immunopathology in respiratory viral infections.

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“…et al, 2005). RSV causes upper respiratory tract infection with frequent involvement of the lower airway and represents the main cause of hospitalization due to bronchiolitis (Hall, 2001;McNamara et al, 2005;Stein et al, 1999). There is currently no vaccine against this virus and ribavirin, the only licensed antiviral, has shown little or no benefit and is not used routinely (Krilov, 2011).…”

Section: Introductionmentioning

confidence: 99%

A new real-time RT-qPCR assay for the detection, subtyping and quantification of human respiratory syncytial viruses positive- and negative-sense RNAs

Essaidi-Laziosi

Lyon

Mamin

et al. 2016

Journal of Virological Methods

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a b s t r a c tHuman respiratory syncytial virus (RSV) is a major health problem and the main cause of hospitalization due to bronchiolitis. RSV is divided into two antigenic subgroups, RSV-A and -B that co-circulate worldwide. Rapid and sensitive detection is desirable for proper patient handling while assessment of viral load may help to evaluate disease severity and progression. Finally RSV subtyping is needed to determine the prevalence and pathogenicity of each RSV subgroup, as well as their sensitivity to treatment. In this study, we took into account the most recent circulating RSV variants and designed two quantitative TaqMan one-step RT-PCR assays to detect and quantify both RSV subgroups separately. Standard dilutions of transcripts of positive and negative polarities were included in the assay validation to assess potential differences in sensitivity on negative-sense genomes and positive-sense RNAs. In addition, RSV detection in respiratory specimens of different types and sampled in different populations was compared to commercially available RSV diagnostic tools. Altogether, the RSV-A and -B assays revealed sensitive and quantitative over a wide range of viral loads, with a slight improved sensitivity of the RSV-B assay on positive sense transcripts, and allowed accurate RSV subtyping. We thus provide a useful tool for both RSV diagnostics and research.

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Production of Chemokines in the Lungs of Infants with Severe Respiratory Syncytial Virus Bronchiolitis

Abstract: CXC chemokines predominate within the RSV-infected lung. Much of this response comes from inflammatory cells within the lower respiratory tract. Chemokine response patterns vary over time, possibly indicating different cellular sources for individual chemokines in the RSV-infected lung.

Cited by 165 publications

References 42 publications

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

In vitro modeling of respiratory syncytial virus infection of pediatric bronchial epithelium, the primary target of infection in vivo

Distinctive and critical roles for cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in mice

A new real-time RT-qPCR assay for the detection, subtyping and quantification of human respiratory syncytial viruses positive- and negative-sense RNAs

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